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Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis.

ABSTRACT: Background:Endometrial cancer (EC) is one of the female malignant tumors. Endometrial cancer predominately affects post-menopausal women. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression. Methods:Download the gene expression profile from Gene Expression Omnibus (GEO). Calculate raw expression data according to pre-processing procedures. We performed the "limma" R language package to screen DEGs between Endometrial cancer tissue samples and normal uterus tissue samples. Enrichment of the functions and pathways was analyzed by using clusterprofiler. We utilized Search Tool for the Retrieval of Interacting Genes Database (STRING) to assess protein-protein interaction (PPI) information, and then we used plug-in Molecular Complex Detection (MCODE) to screen hub modules of PPI network in Cytoscape. We also performed functional analysis on the genes in the hub module by using clusterprofiler. Next, we utilized the "WGCNA" package in R to establish co-expression network for the DEGs. The Venn diagram was performed to overlap the gene in key module and hub PPI cluster. We validated the key genes in TCGA, GEPIA, UALCAN and Immunohistochemistry staining obtained from The Human Protein Atlas database. And then we did ROC curve analysis by SPSS. Gene set enrichment analysis (GSEA) and mutation analysis were also performed for hub genes. Results:Functional and pathway enrichment analysis demonstrated that the upregulated differentially expressed genes (DEGs) were significantly enriched in CXCR chemokine receptor binding, chemokine activity, chemokine receptor binding, G-protein coupled receptor binding, RAGE receptor binding, cytokine activity, microtubule binding, receptor regulator activity and microtubule motor activity, and the down-regulated genes were highly enriched in collagen binding. After using STRING software to construct PPI network, 30 prominent proteins were identified and the first two significant modules were selected. In co-expression network, 5 EC-related modules were identified. Among them, the turquoise module has the highest correlation with the EC. We further analyzed the genes in the PPI and turquoise module, and selected eleven key genes related to EC after validation of TCGA database, GEPIA, UALCAN and immunohistochemistry. Six of them had mutation significance. Conclusions:In summary, these 11 genes may become new therapy targets for EC treatment.

SUBMITTER: Liu J

PROVIDER: S-EPMC6528324 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis.

Liu JinHui J Zhou ShuLin S Li SiYue S Jiang Yi Y Wan YiCong Y Ma XiaoLing X Cheng WenJun W

Cancer cell international 20190520

<h4>Background</h4>Endometrial cancer (EC) is one of the female malignant tumors. Endometrial cancer predominately affects post-menopausal women. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression.<h4>Methods</h4>Download the gene expression profile from Gene Expression Omnibus (GEO). Calculate raw expression data according to pre-processing procedures. We performed the "limma" R language package to screen DEGs between En ...[more]

PMID: 31139013

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Project description:BackgroundUterine corpus endometrial carcinoma (UCEC) is a common malignant cancer type which affects the health of women worldwide. However, its molecular mechanism has not been elucidated.MethodsTo identify the hub modules and genes in UCEC associated with clinical phenotypes, the RNA sequencing data and clinical data of 543 UCEC samples were obtained from The Cancer Genome Atlas (TCGA) database and then subjected to weighted gene co-expression network analysis (WGCNA). To explore the potential biological function of the hub modules, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Genes differentially expressed in UCEC were screened according to TCGA data using the "gdcDEAnalysis" package in R (The R Foundation for Statistical Computing). After intersecting with hub genes, the shared genes were used for further survival analyses. The relationship between gene expression level and clinical phenotype was analyzed in the TCGA-UCEC cohort in The University of ALabama at Birmingham CANcer data analysis Portal and the Human Protein Atlas. The microarray data set GSE17025 was also analyzed to validate the gene expression profiles.ResultsThere were 19 coexpression modules generated by WGCNA. Among them, 2 modules with 198 hub genes were highly correlated with clinical features (especially histologic grade and clinical stage). Meanwhile, 4,003 differentially expressed genes (DEGs) were screened out, and 164 DEGs overlapped with hub genes. Survival analyses revealed that high expression of GINS4 and low expression of ESR1 showed a trend of poor prognosis. Further analyses demonstrated that both messenger RNA (mRNA) and protein expression profiles of GINS4 and ESR1 were significantly associated with UCEC development and progression in TCGA and GSE17025 cohorts.ConclusionsBased on the integrated bioinformatic analyses, our data indicated that GINS4 and ESR1 might serve as potential prognostic markers and targets for UCEC therapy.

Project description:BackgroundOral cancer (OC) is a common and dangerous malignant tumor with a low survival rate. However, the micro level mechanism has not been explained in detail.MethodsGene and miRNA expression micro array data were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and miRNAs (DE miRNAs) were identified by R software. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis were used to assess the potential molecular mechanisms of DEGs. Cytoscape software was utilized to construct protein-protein interaction (PPI) network and miRNA-gene network. Central genes were screened out with the participation of gene degree, molecular complex detection (MCODE) plugin, and miRNA-gene network. Then, the identified genes were checked by The Cancer Genome Atlas (TCGA) gene expression profile, Kaplan-Meier data, Oncomine, and the Human Protein Atlas database. Receiver operating characteristic (ROC) curve was drawn to predict the diagnostic efficiency of crucial gene level in normal and tumor tissues. Univariate and multivariate Cox regression were used to analyze the effect of dominant genes and clinical characteristics on the overall survival rate of OC patients.ResultsGene expression data of gene expression profiling chip(GSE9844, GSE30784, and GSE74530) were obtained from GEO database, including 199 tumor and 63 non-tumor samples. We identified 298 gene mutations, including 200 upregulated and 98 downregulated genes. GO functional annotation analysis showed that DEGs were enriched in extracellular structure and extracellular matrix containing collagen. In addition, KEGG pathway enrichment analysis demonstrated that the DEGs were significantly enriched in IL-17 signaling pathway and PI3K-Akt signaling pathway. Then, we detected three most relevant modules in PPI network. Central genes (CXCL8, DDX60, EIF2AK2, GBP1, IFI44, IFI44L, IFIT1, IL6, MMP9,CXCL1, CCL20, RSAD2, and RTP4) were screened out with the participation of MCODE plugin, gene degree, and miRNA-gene network. TCGA gene expression profile and Kaplan-Meier analysis showed that high expression of CXCL8, DDX60, IL6, and RTP4 was associated with poor prognosis in OC patients, while patients with high expression of IFI44L and RSAD2 had a better prognosis. The elevated expression of CXCL8, DDX60, IFI44L, RSAD2, and RTP44 in OC was verified by using Oncomine database. ROC curve showed that the mRNA levels of these five genes had a helpful diagnostic effect on tumor tissue. The Human Protein Atlas database showed that the protein expressions of DDX60, IFI44L, RSAD2, and RTP44 in tumor tissues were higher than those in normal tissues. Finally, univariate and multivariate Cox regression showed that DDX60, IFI44L, RSAD2, and RTP44 were independent prognostic indicators of OC.ConclusionThis study revealed the potential biomarkers and relevant pathways of OC from publicly available GEO database, and provided a theoretical basis for elucidating the diagnosis, treatment, and prognosis of OC.

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Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis.

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Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis.

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